1-alkoxy-4-hydroxy-2, 3-dicarbalkoxy naphthalenes



Patented May 18, 1948 1-ALKOXY-4-HYDROXY-2,3-DICARB- ALKOXY NAPHTHALENESAugust H. Homeyer, St. Louis, Mo., assignor to Mallinckrodt ChemicalWorks, St. Louis, Mo., a corporation of Missouri No Drawing. Originalapplication July 14, 1941,

Serial No. 402,427. Divided and this application February 10, 1944,Serial No. 521,848

4 Claims. 1

will be in part obvious and in part pointed out hereinafter.

The invention accordingly comprises the elements and combinations ofelements, the proporti'ons thereof, steps and sequence of steps, andfeatures of composition and synthesis, analysis, or'metathesis, whichwill be exemplified in the substances, products and processeshereinafter described, and the scope of the application of which will beindicated in the following claims.

According to the present invention new derivatives of naphthalene,having hydroxyl groups either free or etherified in the 1 and 4positions, anda carboxyl group or groups free or esterified in the 2and/ or 3 positions, are provided, together with new methods forpreparing compounds of this type.

lilxmsnuzaszl 1,4-dihydrory-2,3-dicarbethoa:ynaphthalene 9 Sodium metal(24 g.) was dissolved in anhydrous alcohol (500 ml.) in a 2-liter,3-necked flask, fitted with a. stirrer, condenser, and dropping funnel;and heated on an oil bath. Alcohol (310ml) was distilled off, at whichtime the sodium ethylate which was formed was beginning to cake. Diethylphthalate (400 ml.) was added and the mixture was stirred and heatedwhile diethyl succinate (88 g.) was added dropwise during one andone-half hours. w

The reaction mixture-became dark red during theaddition of the diethylsuccinate and about 200ml. of alcohol were obtained as distillate. Thereaction mixture was heated three quarters of an hour longer at 115 C.inside temperature. .After cooling, water (500 ml.) was added to theflask and dissolved the solid. The mixtureawas trans-T A acid ofcrystallization, filtered, washed and dried.

ferred to a separator, benzene (300 ml.) was added, and the aqueousphase was separated. The organic layer was reextracted with dilutesodium hydroxide solution containing a small amount of sodiumhyposulfite. The combined aqueous extracts were acidified to Congo withhydrochloric acid. A dark red oil separated and was isolated bydecanting the aqueous layer which was then extracted with ether. Theether extract was evaporated and the oil obtained was added to the mainportion. This soon solidified to a red mass and was recrystallized fromalcohol containing a little concentrated hydrochloric acid. Colorlesscrystals of 1,4-dihydroxy-2,3-dicarbethoxynaphthalene in a yield of 48%of the theoretical were obtained. The crystals melted at 62-63 C.

EXAMPLE 2 1,4-dihydroxynaphthoic acid-2 1 ,4-dihydroxy-2,3-dicarbethoxynaphthalene 24 g.) was dissolved in a solution of sodiumhydroxide (24 g.) in water ml.) containing about g. of sodiumhyposulfite, and kept over night. The orange-colored solution was pouredonto a mixture of ice and concentrated hydrochloric acid (about 50 ml.).Carbon dioxide was evolved and ayellow solid separated. It was filteredoff and recrystallized from glacial acetic acid. The prod not was warmedwith water to remove the acetic The yield of 1,4-dihydroxynaphthoicacid-2 was 87% of the theoretical. It decomposed at about 201 C. andrecrystallized from dilute alcohol as long needles' Neutral equivalent:Calculated, 204; found, 199.

EXAMPLE 3 1,4-dimethoxy+2,3-dicarbethoxynaphthwlene Sodium metal (5.5g.) was dissolved in anhydrousv alcohol (1'75 ml.). 1,4-dihydroxy-2,3-dicarbethoxynaphthalene .(27 g.) was added and methyl iodide (40 g.) waslikewise added. The mixture was keptover night, then refluxedfor fivehours and poured onto ice and a little hydrochloric acid. An oilseparated which was removed and mixed with 'alcohol'( 10 ml.) and cooledin dry ice. After it had solidified petroleum ether was added andthesolid was filtered off.- Upon recrystallization 1,4-dimethoxy2,3-dicarbethoxy naphthalene, having a melting point of 48-49" C., wasobtained.

EXAMPLE 4 1 -mctha:y- 4 -hydro:cy-2,3-dicarbethoxynaphtha- Zene Sodiummetal (1.4 g.) was dissolved in anhydrous alcohol (150 ml.) and1,4--dihydroxy-2,3-di carbethoxynaphthalene (18 g.) was added. Methyliodide (7 ml.) was introduced and the mixture, after being kept overnight, was refluxed four hours. It was neutral to phenolphthalein. Whenpoured into a mixture of ice and a little hydrochloric acid, a waxyyellow solid separated. Recrystallization from alcohol yielded l-methoxy4 hydroxy 2.3 dicarbethoximaphthalene melting at 8081 C.

EXAMPLE 5 1 .4- dimethoazy-2,3-dicarbethorynaphthalene1-Methoxy-4-hydroxy-2,3 dicarbethoxynaphthalene (6.3 g.) was methylatedwith sodium ethylate (0.6 g. sodium) and methyl iodide (3 ml.) inanhydrous alcohol (50 ml.). Lei-dimethoxy- 2,3-dicarbethoxynaphthalenewas obtained.

EXAMPLE 6 1,4-dimethoxynaphthalene-2,3-dicar-boxylic acid 1, 4 dimethoxy2,3-dicarbethoxynaphthalene (6.5 g.) was added to a solution of sodiumhydroxide (4.5 g.) in Water ml.) and alcohol (40 ml.). After warming onthe steam bath for about an hour the mixture was poured onto ice andhydrochloric acid (25 ml.) The precipitated solid was filtered off and.recrystallized from dilute alcohol. When heated in a capillary tube themelting point of the anhydride of the1,4-dimethoxynaphthalene-2,3-dicarboxylic acid was 202- 204 C. Neutralequivalent of the acid: calculated, 138; found 137.5.

EXAMPLE 7 1-h.ydr0ry--meth-oxynaphthoic acid-3 1-methoxy-4-hydroxy-2,3dicarbethoxynaph thalene (6.5 g.) was dissolved in a solution of sodiumhydroxide (5 g.) in water (75 ml.), refluxed for two hours and kept overnight at 70 C. It was poured onto ice and hydrochloric acid. Carbondioxide was evolved and a pink solid separated. The1-hydroxy-4-methoxynaphthoic acid-3, recrystallized from dilute alcohol,had a melting point of 217-219 C.

EXAMPLE 8 1-hydro:ry-4-methowynaphthoic acid-2 lA-dihydroxynaphthoicacid-2 g.) was dissolved in methyl alcohol (280 g.) and saturated withhydrogen chloride. On heating for three hours, considerable solidmaterial separated. It was then cooled, again saturated with hydrogenchloride and was kept over night. The next day the reaction product waspoured into water (500 ml.) and the precipitate was filtered off anddried. The product was mixed with dilute sodium bicarbonate solution inwhich it partly dissolved. The insoluble portion was extracted withether. The aqueous solution was acidified, yielding a white solid. Uponrecrystallization from acetic acid and from dilute alcohol,1-hydroxy-4-methoxynaphthoic acid-2 was obtained. It decomposed at196-198 C., with sinter'ing at somewhat lower temperatures. i

EXAMPLE 9 M ethyl-1 -hydromy-4-methorynaphthoate-Z The ether extract ofthe sodium bicarbonate solution obtained in the preceding example wasevaporated to dryness, yielding a gray solid which melted at about 137C. Methyl-1-hydroxy-4- methoxynaphthoate-Z, upon recrystallization froma mixture of methyl alcohol and acetic acid and then from acetone, wasobtained, melting at 137-138 C.

EXAMPLE 10 M ethyl l -hydroxy--methoxynaphthoate-2 Diazomethane wasprepared from ethyl-nitrosomethyl-urethane (2.64: g.) and a solution (10ml.) containing 25% by weight of potassium hydroxide in methyl alcohol.The caustic solution was placed in a small flask, warmed on a steambath, while the urethane dissolved in ether was added from a droppingfunnel, the distillate being absorbed in ether, cooled in an ice bath. 1hydroxy-4-methoxynaphthoic acid-2 (1.09 g.) was added, dissolved in amixture of ether (25 ml.) and methyl alcohol (10 ml). After keeping overnight, the ether solution was shaken with dilute hydrochloric acid,dried over calcium chloride and evaporated. Themethyl-l-hydroxyl-methoxynaphthoate-2 obtained melted at 136-138 C.

EXAMPLE '11 Methyl-lA-dimcthomynaphthoate-3 Diazomethane was preparedfrom an ether solution of ethyl-nitroso-methyl-urethane (2.64

g.) and 10 ml. of 25% by weight potassiurrrhy droxide in methyl alcohol.The ethereal distillate of diazomethane was received'in anhydrous. ether(50 ml.) cooled in ice, and l-hydroxy-l-methoxynaphthoic acid-3 (1.1 g.)was added dissolved in ether (25 ml.) and methyl alcohol (115 ml.) Afterstanding over night. the ether solution was shaken:

with dilute hydrochloric acid, washed with'dilute sodium hydroxide,dried and evaporated to dryness. The methyl-lA-dimethoxynaphthoate iicrystallized from dilute; methyl alcohol asv plates. It sublimed in ahigh vacuum at C. and melted at 57-59 0;

EXAMPLE 12 Methyl-1,4dimethoxynaphthoate-3 Methyl-l-hydroxy {lmethoxynaphthoate-Z was methylated with diazomethane in methanolsolution. The diazomethane was in excess. Methyl 1,4 dimethoxynaphthoate3 was ob-' tained.

EXAMPLE 13 Methyl-1,4-dimethoxynaphthoate-3 my copending patent, No.2,428,884. I:

I claim:

1. A compound having the formula I IHl OOaCaHs 2. The method whichcomprises reacting 1,4- dihydroxy 2,3 dicarbethoxynaphthalene withmethyl iodide and the approximately theoretical proportion of sodiumethylate in liquid phase to form 1-methoxy-4-hydroxy-2,3dicarbethoxynaphthalene.

3. A compound having the formula 0 OIY where X, Y and Z are lower alkylradicals. 4. The method of forming a where X, Y and Z are lower alkylradicals, which comprises alkylating a1,4-dihydroxy-2,3-dicarbalkoxynaphthalene in liquid phase with a loweralkyl halide and the approximately theoretical proportion of an alkalimetal alcoholate.

AUGUST H. HOMEYER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 1,551,373 Daudt Aug. 25, 19252,181,119 Caplan Nov. 28, 1939 2,240,034 Caplan Apr. 29, 1941 OTHERREFERENCES Schwerin, Ber. Deut. Chem. Ges, vol. 2'7, pages 112-113.

Nikuni et a1., Chem Abstracts, v01. 34, col. 3259.

Cason et al., J our. Am. Chem. $00,. vol. 63, pages 1256-1258.

Beilstein, 4th ed., vol. 10, pages 442-443, 564.

